TBC1D3C

Summary

TBC1D3C (TBC1 domain family member 3C, HGNC:24889) is a protein-coding gene on chromosome 17q12, encoding TBC1 domain family member 3C (Q6IPX1). Acts as a GTPase activating protein for RAB5.

This gene represents one of a cluster of related genes found on chromosome 17. The proteins encoded by this gene family contain a TBC (Tre-2, Bub2p, and Cdc16p) domain and may be involved in GTPase signaling and vesicle trafficking.

Source: NCBI Gene 414060 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 11 total
• MANE Select transcript: NM_001001418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24889
Approved symbol	TBC1D3C
Name	TBC1 domain family member 3C
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	MGC44903
Ensembl gene	ENSG00000278299
Ensembl biotype	protein_coding
OMIM	610806
Entrez	414060

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000622206

RefSeq mRNA: 1 — MANE Select: NM_001001418 NM_001001418

CCDS: CCDS74045

Canonical transcript exons

ENST00000622206 — 14 exons

Exon	Start	End
ENSE00003716432	38061095	38061189
ENSE00003717269	38066995	38067067
ENSE00003722568	38060081	38060180
ENSE00003722585	38064861	38064941
ENSE00003725936	38059558	38059710
ENSE00003727317	38061903	38062023
ENSE00003729550	38068496	38068634
ENSE00003733900	38063871	38063980
ENSE00003739338	38057693	38058576
ENSE00003742591	38064310	38064417
ENSE00003743330	38060644	38060709
ENSE00003745844	38062567	38062615
ENSE00003747747	38065424	38065463
ENSE00003752129	38066747	38066832

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 75.00.

Top tissues by expression

132 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	75.00	gold quality
apex of heart	UBERON:0002098	68.12	gold quality
right testis	UBERON:0004534	64.91	gold quality
left testis	UBERON:0004533	63.34	gold quality
testis	UBERON:0000473	61.74	gold quality
fundus of stomach	UBERON:0001160	54.38	gold quality
right adrenal gland	UBERON:0001233	52.65	gold quality
bone marrow	UBERON:0002371	52.54	gold quality
sural nerve	UBERON:0015488	51.83	gold quality
bone marrow cell	CL:0002092	50.00	silver quality
right hemisphere of cerebellum	UBERON:0014890	48.87	gold quality
ganglionic eminence	UBERON:0004023	47.70	gold quality
adenohypophysis	UBERON:0002196	47.66	gold quality
lymph node	UBERON:0000029	47.47	gold quality
left uterine tube	UBERON:0001303	47.30	gold quality
muscle of leg	UBERON:0001383	45.38	gold quality
gastrocnemius	UBERON:0001388	44.93	gold quality
gall bladder	UBERON:0002110	44.64	gold quality
upper lobe of left lung	UBERON:0008952	44.64	gold quality
right lobe of liver	UBERON:0001114	44.49	gold quality
cortical plate	UBERON:0005343	44.38	gold quality
blood	UBERON:0000178	44.28	gold quality
body of uterus	UBERON:0009853	44.11	gold quality
urinary bladder	UBERON:0001255	43.72	gold quality
ventricular zone	UBERON:0003053	43.32	gold quality
skeletal muscle tissue	UBERON:0001134	42.96	silver quality
cerebellar hemisphere	UBERON:0002245	42.60	gold quality
lung	UBERON:0002048	42.47	gold quality
cerebellum	UBERON:0002037	42.28	gold quality
cerebellar cortex	UBERON:0002129	42.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting TBC1D3C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-3135A	96.41	65.30	494
HSA-MIR-548AD-3P	94.39	66.04	350

Literature-anchored findings (GeneRIF, showing 2)

• The Tre2 (USP6) oncogene is derived from the chimeric fusion of two genes, USP32 (NY-REN-60), and TBC1D3. (PMID:12604796)
• Decoupling actin assembly from microtubule disassembly by TBC1D3C-mediated direct GEF-H1 activation. (PMID:39467635)

Cross-species orthologs

0 orthologs

Paralogs (45): RABGAP1 (ENSG00000011454), TBC1D22A (ENSG00000054611), TBC1D22B (ENSG00000065491), TBC1D1 (ENSG00000065882), EVI5 (ENSG00000067208), TBC1D25 (ENSG00000068354), TBC1D2 (ENSG00000095383), TBC1D10A (ENSG00000099992), SGSM3 (ENSG00000100359), TBC1D17 (ENSG00000104946), TBC1D13 (ENSG00000107021), TBC1D12 (ENSG00000108239), TBC1D9 (ENSG00000109436), TBC1D30 (ENSG00000111490), TBC1D15 (ENSG00000121749), TBC1D5 (ENSG00000131374), TBC1D14 (ENSG00000132405), TBC1D8B (ENSG00000133138), TBC1D4 (ENSG00000136111), GRTP1 (ENSG00000139835), SGSM2 (ENSG00000141258), EVI5L (ENSG00000142459), TBCK (ENSG00000145348), USP6NL (ENSG00000148429), RABGAP1L (ENSG00000152061), SGSM1 (ENSG00000167037), TBC1D21 (ENSG00000167139), TBC1D2B (ENSG00000167202), TBC1D16 (ENSG00000167291), TBC1D10B (ENSG00000169221), TBC1D10C (ENSG00000175463), TBC1D28 (ENSG00000189375), TBC1D9B (ENSG00000197226), TBC1D8 (ENSG00000204634), TBC1D26 (ENSG00000214946), TBC1D3G (ENSG00000260287), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512)

Protein

Protein identifiers

TBC1 domain family member 3C — Q6IPX1 (reviewed: Q6IPX1)

All UniProt accessions (1): Q6IPX1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a GTPase activating protein for RAB5. Does not act on RAB4 or RAB11.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in pancreas, thymus and testis.

Post-translational modifications. Ubiquitinated by a CUL7-based E3 ligase, which leads to proteasomal degradation. Palmitoylation is required for membrane localization and protects TBC1D3 from ubiquitination.

Miscellaneous. TBC1D3 is encoded by a collection of very similar paralogs with multiple copies of each paralog, some human genomes encoding well over 50 copies depending on ethnic origin of the donor.

RefSeq proteins (1): NP_001001418* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR050302	Rab_GAP_TBC_domain	Family

Pfam: PF00566

UniProt features (10 total): sequence conflict 4, lipid moiety-binding region 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IPX1-F1	60.35	0.24

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 318, 325

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 13 (showing top): GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, MIR335_3P, MIR5585_5P, chr17q12, NAKAYA_B_CELL_FLUARIX_FLUVIRIN_AGE_18_50YO_7DY_UP, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, WP_17Q12_COPY_NUMBER_VARIATION_SYNDROME, GOCC_ENDOSOME, GOMF_GTPASE_ACTIVATOR_ACTIVITY, JIANG_CORE_DUPLICON_GENES

GO Biological Process (0):

GO Molecular Function (1): GTPase activator activity (GO:0005096)

GO Cellular Component (3): endosome (GO:0005768), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

2 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (10): LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Two-hybrid), LOC101060321 (Negative Genetic), LOC101060321 (Negative Genetic)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A6NDS4, A6NER0, A6QPT6, B9A6J9, M3WHG5, O14771, O15482, O15553, O19110, O76081, P0C7X1, P0C7X3, P0C7X4, P35125, P48778, P48967, P79209, Q13670, Q15697, Q2TBC4, Q3T191, Q3UZD7, Q4R2Z8, Q5DRQ5, Q5SSQ6, Q5XFX8, Q69ZB3, Q6DHY5, Q6IPX1, Q6ZMN8, Q8BLR5, Q8BWA8, Q8IYF1, Q8IZP1, Q8JZW5, Q8N7G0

Diamond homologs: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A2AWA9, A6H6A9, A6NDS4, A6NER0, B9A6J9, H2KZZ6, P0C7X1, P35125, Q2M2D7, Q5RAN1, Q5SVR0, Q66K14, Q6DHY5, Q6IPX1, Q80XC3, Q86UD7, Q8IZP1, Q92738, Q9UFV1, Q9Y3P9, A3KGB4, A6QP29, B0R0W9, B7ZAP0, O60343, O60447, O95759, O97790, P58802, P97366, Q0IIM8, Q10496, Q12317, Q12344, Q28CB1, Q3UYK3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

11 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3577 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS111711695 (17:38071988 G>A), RS111828591 (17:38071237 A>C,G), RS111848730 (17:38068539 A>G), RS112625240 (17:38071526 C>T), RS113293589 (17:38071236 G>A,C,T), RS1158410683 (17:38062865 TCA>T), RS1158601797 (17:38070885 C>T), RS1162671292 (17:38071096 C>T), RS1164935579 (17:38070998 C>T), RS1166294406 (17:38063110 T>G), RS1166463112 (17:38070654 TG>T), RS1168731347 (17:38071140 G>A), RS1169440318 (17:38071217 G>A), RS1169848138 (17:38062555 G>A), RS1171801955 (17:38071332 G>C)

Disease associations

OMIM: gene MIM:610806 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_15	Body mass index	3.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	1
2-palmitoylglycerol	increases expression	1
Arsenic	decreases expression, increases abundance	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.